We propose to study the relationship between steroid hormone receptors and function of B-lymphocytes in normal and leukemic (L2C) guinea pigs. The neoplastic lymphocyte may survive longer than normal cells due to some defect in normal maturation and differentiation. Since an early step in the sequence of events which mediates the effect of steroid hormones on their target tissues is believed to be the interaction of the hormones with specific receptor molecules, our approach will be to characterize the glucocorticoid specific receptors of normal guinea pig B-lymphocytes and L2C cells and to relate receptor content and character to function. We will determine the differences or similarities in cytoplasmic and nuclear steroid receptor complexes, the cytoplasmic to nuclear translocation process of the receptor and the nuclear binding characteristics of the receptor of normal B-lymphocytes and the L2C cells. To relate receptor studies to function, the cellular response of B-lymphocytes to mitogen stimulation will be determined in normal and L2C cells as well as the induction of specific proteins which might render the differentiated normal B-lymphocyte resistant to further steroid hormone action. To date there is a lack of information correlating glucocorticoid receptors and, specifically, the B type lymphocyte which is responsible for the humoral immune response. The use of glucocorticoid agonists and antagonists will contribute to the elucidation of the glucocorticoid receptor mechanism in the normal state and in leukemia. These studies are unique since they will make a contribution to our understanding of the normal function of B-lymphocytes and the role glucocorticoids may play in the mediation of the control of cell proliferation.